Traumatic Stress and Alcohol Problems: Between- and Within- Person Associations

描述（由申请人提供）：本申请是对PA-10-255“酒精依赖和相关表型的行为调节机制”的回应，该申请旨在促进对调节机制与酒精依赖之间的关联、赋予酒精依赖风险的遗传和环境因素以及区分酒精依赖与相关外化行为的因素的研究。伊拉克自由行动/持久自由行动退伍军人的拟议研究采用纵向突发设计，模拟创伤后应激障碍症状，酒精依赖和相关的行为问题的动态过程。我们测试的假设，潜在的监管赤字，依赖和其他外化行为之间的分离，和基因x环境的相互作用。PTSD与酒精依赖以及导致社会和职业功能困难的相关外化问题有关（Frueh等人，2001; Hog等人，2007;米尔斯等人，2007; Seal等人，2011年）。研究表明，影响行为调节的缺陷是连接PTSD和酒精相关问题的两个不同途径（米勒等人，2006年）。我们认为这两种途径与不同类型的问题有关。最近关于物质依赖的负强化模型的理论和研究已经强调了情感不稳定性的作用，而不是平均水平的负面情感在依赖性发展中的作用（Baker等人，2004; Simons等人，2009，2010 b; Weinstein等人，2008年）。创伤后应激障碍（PTSD）与明显的不稳定性有关，我们认为正是这种情绪的变异性增加了该人群出现酒精依赖的风险。相反，我们认为与PTSD和酒精使用相关的行为问题是行为去抑制的一个功能。抑制解除介导PTSD和酒精问题之间的关联（米勒等人，2006）并且去抑制主要与酒精相关的行为问题而不是依赖症状相关（Simons等人，2009年; 2010年b）。虽然创伤暴露与创伤后应激障碍和酒精问题的发展有关，但这些相关性在不同的人中存在显着差异。我们假设5-羟色胺转运蛋白连锁多态性区域（5-HTTLPR）的基因型与创伤暴露相互作用，以预测PTSD症状和酒精依赖，以及中介变量，影响不稳定性和行为去抑制。这项研究将测试调控机制的作用 随着时间的推移，症状的增长，通过人x情况影响的结果的急性变化，以及酒精消费对不稳定性和PTSD症状的相互影响。通过整合遗传和环境风险，基本行为调节缺陷，酒精依赖和相关条件的评估，该研究可以提高我们对病因，风险和恢复机制以及治疗变化的潜在机制的理解。

DESCRIPTION (provided by applicant): This application is in response to PA-10-255 "Behavioral Regulation Mechanisms of Alcohol Dependence and Related Phenotypes", which seeks to promote research on associations between regulation mechanisms and alcohol dependence, genetic and environmental factors conferring risk for alcohol dependence, and factors differentiating alcohol dependence from related externalizing behaviors. The proposed study of Operation Iraqi Freedom / Operation Enduring Freedom veterans utilizes a longitudinal burst design to model the dynamic course of PTSD symptoms, alcohol dependence, and associated conduct problems. We test hypotheses regarding underlying regulatory deficits, dissociation between dependence and other externalizing behaviors, and gene x environment interactions. PTSD is related to alcohol dependence as well as associated externalizing problems resulting in difficulties in social and occupational functioning (Frueh, et al., 2001; Hog et al., 2007; Mills et al., 2007; Seal et al., 2011). Research indicates that deficits in affect an behavioral regulation are two distinct pathways linking PTSD and alcohol-related problems (Miller et al., 2006). We propose that these two pathways are associated with different types of problems. Recent theory and research on negative reinforcement models of substance dependence have highlighted the role of affect lability, rather than mean levels of negative affect, in the development of dependence (Baker et al., 2004; Simons et al., 2009, 2010b; Weinstein et al., 2008). PTSD is associated with marked lability, and we posit that it is this variability in mood that confers risk for the development of alcohol dependence in this population. In contrast, we propose that conduct problems associated with PTSD and alcohol use are a function of behavioral disinhibition. Disinhibition mediates associations between PTSD and alcohol problems (Miller et al., 2006) and disinhibition is primarily associated with alcohol-related conduct problems rather than dependence symptoms (Simons et al., 2009; 2010b). Although trauma exposure is associated with the development of PTSD and alcohol problems, there is significant variability in these associations across persons. We hypothesize genotype at the serotonin transporter linked polymorphic region (5-HTTLPR) interacts with trauma exposure to predict PTSD symptoms and alcohol dependence, as well as the intermediary variables, affect lability and behavioral disinhibition. The study will test the role of regulation mechanisms in growth of symptoms over time, acute changes in the outcomes via person x situation effects, and test reciprocal effects of alcohol consumption on lability and PTSD symptoms. By integrating assessment of genetic and environmental risk, basic behavioral regulation deficits, and alcohol dependence and related conditions the study can improve our understanding of etiology, risk and resilience mechanisms, and potential mechanisms of therapeutic change.